Mitochondria is an intracellular organella present in almost all eucaryotic cells and is generally contained in an amount of several hundreds to several thousands per cell. Mitochondria has an elongated elliptic structure surrounded by two layers of an outer layer and an inner layer. As its main roles, it produces adenosine triphosphate (ATP), which is an energy source of cells, through a citric acid cycle and an electron transmitting system and oxidative phosphorylation conjugating both of them and also it plays a primary role in the regulation of cell death. It is said that active oxygen is released from mitochondria to cause decrease in cell function and cell death and it has been reported that the production of active oxygen from mitochondria increases in aged animals.
Although the mechanism of onset of Alzheimer's disease has yet been unclear, there has been obtained a finding which suggests that decrease in mitochondrial function closely relates to the omission of the nerve in Alzheimer's disease. Heretofore, as brain diseases induced by mitochondrial dysfunction, there are known, in addition to Alzheimer's disease, amyotrophic lateral sclerosis (ALS); mitochondrial diseases such as mitochondrial encephalomyopathy; migraine; Parkinson's disease; Alzheimer's disease; ischemic cerebral disorders such as cerebral infarction, hypoxic encephalopathy, and cerebral arteriosclerosis; manic-depressive psychosis; chronic fatigue syndrome; intracranial hypertension induced by hydrocephalus and head injury; normal pressure hydrocephalus; cerebral vasospasm after subarachnoid hemorrhage; prevention of cerebral ischemia at surgery and intravascular surgery; and the like.
Among them, cerebral infarction accounts for about 70% of cerebral stroke and the cerebral stroke is third cause next to malignant neoplasm (cancer) and heart disease in statistics in 2004 and accounts for 12.5% of total number of death. The cerebral infarction is classified into two types depending on the way of blocking a blood vessel. There are cerebral thrombosis wherein the blood vessel undergoes arteriosclerosis and the inner cavity is gradually narrowed and blocked and cerebral embolism wherein thrombus is formed in the heart or a large blood vessel and the thrombus is carried to the brain to block a blood vessel in the brain. The cerebral cells completely died and their recovery is impossible within several minutes when the blood flow is thoroughly shut out. However, since a blood flow from the other blood vessel(s) usually remains to some extent even when one blood vessel is blocked, the blood flow is not suddenly thoroughly shut out. The brain cells gradually die from the area where the blood flow is poor during several hours from the blockage of the blood vessel. In the cerebral thrombosis, the symptoms slowly progress and are completed after 2 to 3 days in some cases but, in the cerebral embolism, the symptoms are suddenly completed and are generally severer than in the case of the cerebral thrombosis. The cerebral infarction is further roughly classified into three types in some cases. There are the following three types: (1) atherothrombotic cerebral infarction wherein a large blood vessel at the neck or in the head is blocked by arteriosclerosis, (2) lacunar infarction wherein a fine blood vessel in the brain is blocked, and (3) cardiogenic cerebral embolism wherein thrombus is formed in the heart owing to atrial fibrillation (one kind of arrhythmia), myocardial infarction, a valvular disease of heart, cardiomyopathy, and the like and reaches the brain.
At the medical examination of the brain infarction, it is important to adequately grasp the neurological symptoms and accurately diagnose a diseased site. A rough neurological examination can be performed within 5 minutes by a medical doctor but, in order to help the diagnosis and determine an adequate therapeutic strategy, examinations such as a CT examination (computer tomography), an MRI examination (magnetic resonance imaging), an ultrasonic Doppler examination, cerebral angiography, and a cerebral blood flow examination have been performed. All these examinations are preoperative diagnosis before treatments and it is a current situation that an examination method capable of judging a diseased site while an operation is performing does not exist.
The treatment of the cerebral infarction varies depending on the type of the cerebral infarction, i.e., atherothrombotic cerebral infarction, lacunar infarction, or cardiogenic cerebral embolism, period of time after its onset, and severity. As special treatments, there may be mentioned a treatment for reducing dropsy of brain, a treatment against thrombus in the blood vessel, a treatment for protecting nerve cells, and the like. As the most effective treatment, a thrombolytic therapy (tissue plasminogen activator) is employed overseas but a thrombolytic agent should be administered within 3 hours after the onset of the cerebral infarction. As a thrombolytic therapy, there is a method of finding out a site where brain blood vessel is blocked by an examination called cerebral angiography and dissolving the thrombus through insertion of a catheter into the site but it is also necessary to perform the method within 3 to 6 hours after the onset of the cerebral infarction. Furthermore, in the case where the thrombolytic therapy is not applicable, there is also a treatment of administering an antiplatelet agent or a blood coagulation inhibitor.
However, even when these treatments are performed, there are cases where some aftereffects (consciousness disorder, movement and perception disorder, higher brain function disorder, attentiveness disorder, and emotional disorder) may remain due to delay of the performance or mistake of the performance and thus it is an actual situation that a medical agent capable of treating the diseased site simultaneously to thrombolytic therapy does not exist.
On the other hand, when δ-aminolevulinic acid (ALA) or a derivative thereof is administered, it is known that derived protoporphyrin IX is accumulated in a tumor and is effective for intraoperative diagnosis and treatment (Patent Document 1 and Non-Patent Document 1). Moreover, when δ-aminolevulinic acid (ALA) or a derivative thereof is administered to the head in combination with an iron compound, it is known to exhibit a hair growth effect (Patent Document 2). However, an action of δ-aminolevulinic acid (ALA) or a derivative thereof on cerebral diseases has not been reported.    Patent Document 1: JP-A-11-501914    Patent Document 2: WO2005/105022    Non-Patent Document 1: Nou Shinkei Geka (Cranial Nerve Surgery), 29(11): 1019-1031, 2001